Preimplantation Genetic Testing Fails to Improve IVF Birth Rates

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Preimplantation genetic testing for aneuploidy (PGT-A) during in vitro fertilization (IVF) did not lead to better chances of having a baby than conventional IVF among women with a good chance of a live birth, Chinese researchers found in a multicenter randomized trial.

Among women who had at least three good-quality blastocysts, PGT-A did not improve cumulative live birth rates compared to conventional IVF methods (77.2% vs 81.8%, absolute difference -4.6%), reported Zi-Jiang Chen, MD, PhD, of Shandong University in China, and colleagues.

Additionally, time to live birth and the number of embryos transferred to result in a birth were similar in both the genetic testing and conventional groups (1.2 vs 1.3 embryos), the researchers wrote in the New England Journal of Medicine.

“If you are someone who is in a good prognosis group … and you have three blastocysts, it is in your best interest to not do the genetic testing,” Richard Paulson, MD, director of USC Fertility in Los Angeles, who was not involved in this study, told MedPage Today.

Alan Penzias, MD, a reproductive endocrinologist at Boston IVF, who was also not involved in this trial, agreed. He said that the findings affirm smaller, previous retrospective and prospective trials that have found little benefit of testing in young, good-prognosis patients.

“I think that many times people have a lot of belief that using this technology will improve their outcomes if they’re young and healthy,” Penzias told MedPage Today. “Since the biopsy in this case does not fix the embryo, it’s not very surprising then that testing in the young, healthy population doesn’t get you a better pregnancy outcome.”

Penzias added that this data will improve patient counseling around genetic testing, as clinicians can present evidence about both cumulative live birth rates and potential risk of miscarriage to help patients make an informed decision.

Chen and colleagues noted that because the presence of aneuploidy increases the odds of implantation failure or spontaneous abortion, preimplantation genetic testing was introduced in an attempt to improve embryo selection and IVF success. But there is a lack of clinical data testing cumulative live birth outcomes among women with a good prognosis, they wrote.

They conducted a randomized controlled trial to compare cumulative birth rates of IVF patients who underwent PGT-A to those who underwent conventional therapy. Patients who had fertility treatment at one of 14 centers in China from July 2017 to June 2018 were included. They were followed up for 1 year after randomization.

All couples included in the study were diagnosed with subfertility, were undergoing their first IVF cycle, and had a good prognosis for live birth (i.e., ages 20 to 37 and had three or more good-quality blastocysts available). Couples were excluded if women had a known uterine abnormality or contraindication to pregnancy, if they planned to undergo genetic screening for disease or other parental chromosomal structural rearrangements, or if they used donor eggs or sperm.

In each cycle, a single frozen embryo transfer was performed with a euploid blastocyst in the genetic testing cohort, and a blastocyst chosen based on morphologic criteria in the conventional group. If live birth was not achieved after the first embryo transfer, subsequent embryo transfers were performed for up to three cycles.

In total, 1,212 women were included in the trial. Of the 1,809 embryos that were screened via genetic testing, nearly 70% were euploid. In both groups, patients had an average of 20 oocytes and seven good-quality blastocysts.

A majority of patients in both trial arms got pregnant after their first embryo transfer. However, more patients in the conventional IVF group needed a second and third embryo transfer to achieve a live birth.

There was a lower likelihood of clinical pregnancy loss among patients who underwent PGT-A compared to those in conventional treatment (8.7% vs 12.6%, respectively; rate ratio 0.69, 95% CI 0.49-0.98), Chen’s group found, but this did not affect overall results, as there were still no differences in time to pregnancy or cumulative live birth rate.

In a post hoc analysis, which included all live births within 1 year from all embryo transfers or other conceptions, there was no significant difference in cumulative live birth rates between the genetic testing cohort and the conventional IVF group (85.3% vs 82.5%, respectively).

Adverse events, including severe ovarian hyperstimulation syndrome, ectopic pregnancy, obstetrical or perinatal complications, and congenital anomalies were also similar between the two groups.

Chen’s group recognized a few limitations. This trial only included a “good prognosis group,” and may not be generalizable to more challenging patient populations. Additionally, it analyzed patients who had up to three embryo transfers, and the findings may not apply to situations where more embryos are available. Finally, the investigators performed intracytoplasmic sperm injection on all embryos, which may not be typical practice across IVF clinics.

Penzias said that this trial provides future investigators with a solid cornerstone to build future studies. Analyzing the impacts of preimplantation genetic testing for aneuploidy on older patients or those with recurrent miscarriage is a logical next step for research, he said, adding that cost of testing should also be assessed.

  • Amanda D’Ambrosio is a reporter on MedPage Today’s enterprise & investigative team. She covers obstetrics-gynecology and other clinical news, and writes features about the U.S. healthcare system. Follow

Disclosures

This trial was funded by the National Natural Science Foundation of China, the National Key Research and Development Program, and the Taishan Scholars Program for Young Experts of Shandong Province.

Chen disclosed no conflicts of interest. One co-author disclosed various ties to industry.

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